Nocturnal hyperactivity induced by prenatal methylazoxymethanol administration as measured in a computerized residential maze

Balduini, Walter; Lombardelli, G.; Peruzzi, G.; Cattabeni, Flaminio; Elsner, J

doi:10.1016/0892-0362(89)90004-4

Cited by 11 publications

(3 citation statements)

References 17 publications

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“…Methylazoxymethanol is a potent genotoxin, and the aglycone of Cycasin (Balduini et al, 1989;Calcagnotto et al, 2002;Cattabeni and Di Luca, 1997). It is found in the seeds and roots of the Cycad plant (Eizirik and Kisby, 1995;Esclaire et al, 1999).…”

mentioning

confidence: 99%

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Bassanini¹,

Hallene²,

Battaglia³

et al. 2007

Neurobiology of Disease

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One of the most common causes of neurological disabilities are malformations of cortical development (MCD). A useful animal model of MCD consists of prenatal exposure to methylazoxymethanol (MAM), resulting in a postnatal phenotype characterized by cytological aberrations reminiscent of human MCD. Although postnatal effects of MAM are likely a consequence of prenatal events, little is known on how the developing brain reacts to MAM. General assumption is the effects of prenatally administered MAM are short lived (24 h) and neuroblast-specific. MAM persisted for several days after exposure in utero in both maternal serum and fetal brain, but at levels lower than predicted by a neurotoxic action. MAM levels and time course were consistent with a different mechanism of indirect neuronal toxicity. The most prominent acute effects of MAM were cortical swelling associated with mild cortical disorganization and neurodegeneration occurring in absence of massive neuronal cell death. Delayed or aborted vasculogenesis was demonstrated by MAM's ability to hinder vessel formation. In vitro, MAM reduced synthesis and release of VEGF by endothelial cells. Decreased expression of VEGF, AQP1, and lectin-B was consistent with a vascular target in prenatal brain. The effects of MAM on cerebral blood vessels persisted postnatally, as indicated by capillary hypodensity in heterotopic areas of adult rat brain. In conclusion, these results show that MAM does not act only as a neurotoxin per se, but may additionally cause a short-lived toxic effect secondary to cerebrovascular dysfunction, possibly due to a direct anti-angiogenic effect of MAM itself.

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confidence: 99%

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Bassanini¹,

Hallene²,

Battaglia³

et al. 2007

Neurobiology of Disease

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“…1972;Seo et al, 1979;Kiyono et al, 1980;Hanada et al, 1982;Cannon-Spoor andFreed, 1984: Vorhees et al, 1984;Plonsky et al, 1985) and motor impairment (Ciafalo et al, 1971: Yamamoto andTanimura, 1989) were observed. Spontaneous motor activities in MAM-treated rats showed significant increases only during night time, but not daytime (Nagayoshi et al, 1986: Sanberg et al, 1987Balduini et al, 1989). It is suggested that significant elevations of monoamine concentrations in the CH of MAM-treated rats may underlie the hyperactivity of the microenlcephalic rat.…”

Section: Neurochemical Correlates Of Abnormal Motor Activity In Mam-tmentioning

confidence: 99%

Neurochemical Correlates of Learning Impairment in Microen‐cephalic Rats Induced by Methylazoxymethanol Acetate*

Tamaru

1994

Congenital Anomalies

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Newborn infants with histogenetic brain malformations can be long‐lived with mental retardation, which is considered a major problem in social medicine. Among these infants with mental retardation, many cases are accompanied by microencephaly. Experimentally induced microencephaly in rats presents a useful model for understanding human cerebral disorders. We have studied how neurochemical changes in the brains of microencephalic rats induced by prenatal treatment with methylazoxymethanol acetate (MAM) can affect their learning abilities. We reported that densities of monoaminergic transmitters in the atrophic cerebral hemisphere (CH; consisting of cerebral cortex and hippocampus) of MAM rats was markedly elevated, but that their total quantity per CH unchanged. As for the ability of operant discrimination learning, MAM rats could discriminate tasks. However, excitatory amino acid receptors, in which N‐methyl‐D‐aspartate (NMDA) is well known to be involved in spatial memory, showed decreased total binding in the CH of MAM‐treated rats. Spatial recognition ability evaluated using an 8‐armed radial maze task was impaired. These results suggest that the condensation of monoaminergic terminals in the atrophic CH of MAM rats may compensate for disability in discrimination learning, but the significant reduction of NMDA receptors may impair spatial memory in MAM rats.

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“…Among the numerous etiologies and conditions related to developmental disabilities in humans, the condition of microcephaly has historically been associated with mental retardation (Cowie, 1987). Methylazoxymethanol (MAM)-induced microencephalic rats show some of the neurological abnormalities present in the cortical, hippocampal, and striatal brain regions of humans with microcephaly (Balduini et al, 1986) and exhibit behaviors representative of some of the aberrant behaviors displayed by individuals with mental retardation (nocturnal hyperactivity and the stereotyped behavior of maintained rearing) (Archer et al, 1988; Balduini, Lombardelli, Peruzzi, Cattabeni, & Elsner, 1989; Kiyono, Seo, & Shibagaki, 1980; Loupe, Stodgell, & Tessel, 1992; Rodier, 1986; Sanberg, Moran, & Coyle, 1987; Sanberg, Moran, Kubos, Anterno, & Coyle, 1983; Vorhees, Fernandez, Dumas, & Haddad, 1984). The offspring also have shown learning deficits in tasks involving multiple choices and reversals of previously learned responses (Cannon-Spoor & Freed, 1984; Loupe, Schroeder, & Tessel, 1995; Mohammed, Jonsson, Soderberg, & Archer, 1986).…”

mentioning

confidence: 99%

Effects of neuroleptic and anticonvulsant drugs on repeated acquisition learning in microencephalic and normal rats.

Loupe¹,

Schroeder²,

Tessel³

1997

Experimental and Clinical Psychopharmacology

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Neuroleptic and anticonvulsant drugs are used to reduce the occurrence of aberrant behaviors, seizures, or both in individuals with mental retardation. However, their use may disrupt the learning of desired skills, and the extent to which anatomical (e.g., microencephaly) or biochemical abnormalities or both in such individuals alter the effects of drugs on learning is not known. In this study, the effects of neuroleptics and anticonvulsants on learning and performance in a repeated acquisition task in methylazoxymethanol-induced microencephalic and saline control rats were assessed. Thioridazine was more potent in microencephalic rats than in control rats in increasing errors and decreasing response rates. Clozapine was equally potent in both microencephalic and control rats in increasing errors and decreasing response rates. The effect of carbamazepine was biphasic in both rat groups: Low doses decreased errors and increased response rates, whereas higher doses did the opposite.

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Nocturnal hyperactivity induced by prenatal methylazoxymethanol administration as measured in a computerized residential maze

Cited by 11 publications

References 17 publications

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Neurochemical Correlates of Learning Impairment in Microen‐cephalic Rats Induced by Methylazoxymethanol Acetate*

Effects of neuroleptic and anticonvulsant drugs on repeated acquisition learning in microencephalic and normal rats.

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